The liver in pregnancy

Chapter 21 The liver in pregnancy



Michelle Lai, MD, MPH, Jacqueline L. Wolf, MD



Key Points



1 Liver diseases in pregnancy include those that occur exclusively in pregnancy and those that occur coincidentally in pregnancy or are present at the time of pregnancy.

2 Normal physiologic changes in pregnancy may alter the normal range for liver biochemical tests (Table 21.1).

3 Important clues to the diagnosis are found in the history and physical examination.

4 Laboratory findings with particular importance to diagnosing liver disease in pregnancy are proteinuria, hyperuricemia, elevated serum bile acid levels, thrombocytopenia, and anemia.

5 Abdominal ultrasonography may be helpful. Liver biopsy is rarely necessary, but it may be diagnostic for acute fatty liver of pregnancy.

6 Timely diagnosis and hence appropriate treatment are critical to outcome. Delivery of the infant is indicated for severe pre-eclampsia, eclampsia, acute fatty liver of pregnancy, and HELLP (hemolysis, elevated liver tests, low platelets) syndrome, and immunization is indicated in infants born to mothers with hepatitis B.

7 Although women with chronic liver disease may have more trouble conceiving, pregnancy has no adverse effect on the progression of liver disease.

TABLE 21.1 Changes in liver biochemical test levels in normal pregnancy











































Test Change Trimester of maximum change
Albumin ↓ 10%–60% Second
Gamma globulins None to slight ↓ Third
Fibrinogen ↓ 50% Second
Transferrin ↓ Third
Bilirubin None —
Alkaline phosphatase ↓ Two- to fourfold Third
AST None —
ALT None —
Cholesterol ↓ Twofold Third

↓, increase; ↓, decrease; ALT, alanine aminotransferase; AST, aspartate aminotransferase.


From Olans LB, Wolf JL. Liver disease in pregnancy. In: Carlson KJ, Eisenstat SA, eds. The Primary Care of Women, 2nd edn. St. Louis: Mosby–Year Book; 2003:531–539.



Overview



1. Liver diseases in pregnancy consist of the following:
image Those that occur exclusively during pregnancy

image Those that occur coincidentally in pregnancy or are present at the time of pregnancy

2. The approach to the pregnant patient with abnormal liver biochemical test levels should include thorough history taking and physical examination.

3. Liver disorders unique to pregnancy include the following:
image Hyperemesis gravidarum

image Intrahepatic cholestasis of pregnancy (IHCP)

image Acute fatty liver of pregnancy (AFLP)

image Pre-eclampsia/eclampsia

image HELLP (hemolysis, elevated liver tests, low platelets) syndrome

image Hepatic rupture

4. Liver disorders that occur coincidentally with pregnancy include viral hepatitis, Budd–Chiari syndrome, cholelithiasis, and cholecystitis, Wilson disease, and autoimmune hepatitis (AIH).


Approach to the Pregnant Patient



History



1. Relation to time of gestation (Table 21.2)

2. Pruritus
image Characteristic of IHCP

image Affects palms of hands and soles of feet initially, then elsewhere

3. Nausea and vomiting
image Occurs in 50% to 90% of all pregnancies

image Key feature of hyperemesis gravidarum

image When associated with headache and peripheral edema may indicate pre-eclampsia

image When associated in late pregnancy with abdominal pain, with or without hypotension, may indicate hepatic rupture

4. Abdominal pain
image The location, character, duration, and factors that induce or relieve pain should be noted

image Right upper quadrant or midabdominal pain in late pregnancy may have ominous implications. Consider cholelithiasis, AFLP, hepatic rupture, and pre-eclampsia

5. Jaundice
image Note the relation of jaundice to the onset of other symptoms

image Jaundice follows pruritus in IHCP

6. Systemic symptoms
image Headache, peripheral edema, foamy urine, oliguria, and neurologic symptoms may occur in pre-eclampsia

image Fever, malaise, and a change in stools may indicate infection such as hepatitis

image Easy bruisability may occur in HELLP syndrome

image Weight loss or gain or dizziness may occur with liver disease in pregnancy

7. History of past pregnancy and birth control use
image Note the time of onset of symptoms in previous pregnancies

image Note the outcome of previous pregnancies

image A history of jaundice with previous birth control use is a risk factor for IHCP

8. Relevant pregnancy-related factors
image Multiple versus single gestation (Table 21.3)

image Primiparous versus multiparous

image Medications

TABLE 21.2 Differential diagnosis of elevated serum aminotransferase levels and/or jaundice according to trimester of pregnancy






















































Trimester Differential diagnosis
First Hyperemesis gravidarum
  Gallstones
  Viral hepatitis
  Drug-induced hepatitis
  Intrahepatic cholestasis of pregnancy∗
Second Intrahepatic cholestasis of pregnancy
  Gallstones
  Viral hepatitis
  Drug-induced hepatitis
  Pre-eclampsia/eclampsia∗
  HELLP syndrome∗
Third Intrahepatic cholestasis of pregnancy
  Pre-eclampsia/eclampsia
  HELLP syndrome
  Acute fatty liver of pregnancy
 
Hepatic rupture

Gallstones

Viral hepatitis

Drug-induced hepatitis

HELLP, hemolysis, elevated liver tests, low platelets.


∗ Uncommon in this trimester.


From Olans LB, Wolf J. Liver disease in pregnancy. In: Carlson KJ, Eisenstat SA, eds. The Primary Care of Women, 2nd edn. St. Louis: Mosby–Year Book; 2003:531–539.


TABLE 21.3 Rates of recurrence of pregnancy-associated liver disease in subsequent pregnancies


















Disease Rate of recurrence
Intrahepatic cholestasis of pregnancy 40%–70%
HELLP syndrome 4%–27%
Acute fatty liver of pregnancy 20%–70% in carriers of LCHAD mutation
Pre-eclampsia 2%–43%

HELLP, hemolysis, elevated liver tests, low platelets; LCHAD, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase.



Physical examination



image Normal findings that occur in pregnancy include spider telangiectasias and palmar erythema

image Abnormal findings that occur with liver disease in pregnancy are jaundice, hepatomegaly, hepatic tenderness, friction rub or bruit, splenomegaly, Murphy’s sign, and diffuse excoriations

image Systemic findings that may occur with liver disease in pregnancy are hypertension, orthostatic hypotension, peripheral edema, asterixis, hyperreflexia or other neurologic findings, ecchymoses, and petechiae


Diagnostic tests



image The only major restrictions compared with the nongravid state are radiation and gadolinium exposures

image Routine blood chemistry tests and a blood count are helpful. Uric acid levels are often elevated in AFLP and may be elevated in pre-eclampsia

image Hemolysis and a low platelet count occur in HELLP syndrome. Disseminated intravascular coagulation (DIC) with a low fibrinogen level, increased fibrin split products, and an elevated partial thromboplastin time may also occur in HELLP syndrome

image Elevations in the serum bile acid level occur before or are concurrent with the onset of IHCP

image Amylase and lipase levels should be checked in a patient with abdominal pain

image If viral hepatitis is suspected, serologic tests should be checked for the following: hepatitis A (immunoglobulin M [IgM] and IgG antibody to hepatitis A virus [anti-HAV]); hepatitis B (surface antigen [HBsAg] and antibody, core antibody, and, if HBsAg is positive, e antigen and antibody); hepatitis C (antibody to hepatitis C virus [anti-HCV] and possibly HCV RNA). If the patient has traveled to an endemic area, consider testing for hepatitis E (see Chapter 3)

image The benefits of endoscopy, including endoscopic retrograde cholangiopancreatography (ERCP), should be weighed against the risks in pregnancy. Risks include fetal hypoxia from sedative drugs or positioning. Sedative medications and radiation exposure should be minimized

image Abdominal ultrasonography is safe and useful

image Although abdominal computed tomography (CT) is more sensitive than abdominal ultrasonography for hepatic rupture and may yield more information, radiation exposure and the stability of the patient should be considered in decisions about the choice of imaging test

image Angiography is rarely needed for hepatic rupture

image Magnetic resonance imaging (MRI) is probably safe, although this is not conclusively proven. Gadolinium should not be used in pregnancy


Liver Disorders Unique to Pregnancy


See Table 21.4 for the laboratory findings associated with these disorders.



TABLE 21.4 Results of laboratory tests in pregnancy-associated liver disease

image


Hyperemesis gravidarum



1. Definition: Intractable vomiting in pregnancy that leads to dehydration, electrolyte disturbances, weight loss of 5% or more, and nutritional deficiencies.

2. Epidemiology
image Most common in first trimester

image Incidence: 0.3% to 2%

image Risk factors: age less than 25 years, preexisting diabetes mellitus, hyperthyroidism, overweight, primiparity, multiple gestations, prior history of hyperemesis gravidarum, and molar pregnancy

3. Etiology: Thought to be multifactorial involving immunologic, hormonal, and psychological factors.

4. Clinical and laboratory features
image Liver biochemical test abnormalities in 50% of patients

image Serum alanine aminotransferase (ALT) elevations generally 1- to 3-fold but may reach 20 times the upper limit of normal

image Occasional serum alkaline phosphatase and bilirubin elevations

image Concomitant hyperthyroidism in 50%

5. Diagnosis: clinical.

6. Treatment: Supportive with rehydration, vitamin supplementation, small and frequent low-fat meals, and antiemetics (e.g., metoclopramide 10 to 30 mg orally four times daily or 10 mg intramuscularly or intravenously every 4 to 6 hours or ondansetron 4 to 8 mg orally every 8 hours or 8 mg intravenously every 4 to 8 hours); total parenteral nutrition possibly needed in severe cases.

7. Outcome: Observed lower rate of spontaneous abortion, but also lower birth weights and increased incidence of congenital hip dysplasia in infants.


Intrahepatic cholestasis of pregnancy



1. Definition: Reversible form of cholestasis characterized by intense pruritus in pregnancy, elevated serum ALT and fasting serum bile acid levels, and spontaneous relief of symptoms and signs within 4 to 6 weeks after delivery.

2. Epidemiology
image More common in late second or third trimester, but can occur in any trimester

image Incidence: 0.01% to 2%, with higher incidence in South Asian, South American, and Scandinavian populations; highest incidence (up to 27%) in Chilean Araucanian Indians

image Risk factors: progesterone use in pregnancy, past medical or family history of IHCP, and personal history of intrahepatic cholestasis resulting from oral contraceptive or estrogen ingestion

3. Etiology: Multifactorial, including genetic, hormonal, and environmental factors. Theories include the following:
image Gene variants of hepatocanalicular transport proteins (ATP-binding cassette [ABC] transporter B4 = phosphatidylcholine floppase, ABC transporter B11 = bile salt export pump, ABC transporter C2 = conjugated organic anion transporter, ATP8B1 = FIC1) and their regulators (e.g., the bile acid sensor farnesoid X receptor, FXR) found in some patients; incidence of IHCP increased in mothers of children with progressive familial intrahepatic cholestasis (PFIC) type 3

image Inherited sensitivity to estrogens

image Association with low serum selenium levels; decreasing incidence in Chilean population linked to increases in serum selenium levels

4. Clinical and laboratory features
image Jaundice in 25% of patients and following the onset of pruritus

image Elevated serum aminotransferase levels (up to four-fold), serum bile acid levels (30–100x), mono- or disulfated progesterone metabolites (particularly 3- and 5-alpha isomers), and occasionally serum cholesterol and triglyceride levels

image Liver biopsy (not usually indicated) specimens reveal cholestasis with minimal hepatocellular necrosis

5. Diagnosis: clinical.

6. Treatment

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Jun 4, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on The liver in pregnancy

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